The objectives of this project are to delineate the cellular site(s) and mechanisms of action of ethanol in mammalian brain in an effort to understand what CNS changes may underly the effects of chronic alcohol exposure. We intensively study drug effects at the level of the cerebellar Purkinje cells in rats. 1) Acute, peripherally administered ethanol has an acute, possibly indirect, activating effect on the spontaneous occurrence of climbing fiber splices to these neurons. Chronic ethanol treatment (by automated gavage or chronic atmospheric exposure sufficient to produce blood levels of 150 mg/dl) and acute withdrawal results in a significant reduction of Purkinje cell firing and with decreased frequency of climbing fiber discharges. In order to provide a pharmacological comparison of these effects of ethanol, we also explored under similar experimental conditions the effects of chronic treatment with the tricyclic anti-depressant desmethylimipramine and with Li. Single acute doses of DMI of Li also slow Purkinje cell firing. Purkinje cell firing patterns may provide a sensitive index to the site and mechanisms of adaptation to chronic ethanol exposure.